Certain 1,3,4-thiadiazole-2-sulfonamide compounds can be employed to combat unwanted vegetation both pre- and post-emergently.
Effective compounds have the structural formula ##STR1## in which R.sup.1 and R.sup.2 are individually selected from the group consisting of hydrogen, alkyl, alkoxy, cycloalkyl, cyanoalkyl, alkoxyalkyl, alkenyl and alkynyl wherein the alkyl, alkenyl and alkynyl moieties contain from one to six carbon atoms; and heterocyclic structures in which R.sup.1 and R.sup.2 together form an alkylene or oxyalkylene chain with two to five carbon atoms; R.sup.3 is hydrogen or C.sub.1 -C.sub.4 alkyl; R.sup.4 is hydrogen or C.sub.1 to C.sub.6 alkyl; R.sup.5 is selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, and C.sub.3 to C.sub.6 cycloalkyl; and X is oxygen or sulfur.
The herbicidal properties of the 1,3,4-thiadiazole-2-sulfonamide structures defined above and various preparatory methods are detailed in U.S. Pat. Nos. 4,021,225 and 3,824,247 which are incorporated herein by reference.
In these patents, although many specific compounds are disclosed having a high degree of phytotoxicity and varied selectivity, it has been recognized that one of the compounds of the disclosed class namely 5-[[dimethylamino)carbonyl]-methylamino]-N,N-dimethyl-1,3,4-thiadiazole-2- sulfonamide, is an unusually effective herbicide of the type which is used industrially to prevent growth of weeds in railroad right-of-ways and in other areas where uncontrolled growth of vegetation is undesirable.
U.S. Pat. No. 4,021,225 recognized that on the basis of disclosures in the chemical literature, particularly Roblin and Clapp, (J. Am. Chem. Soc. 72 4890 (1950), the presence of a free amine function on the thiadiazole molecule precludes the conversion of the mercapto group to the corresponding sulfonyl chloride by oxidative chlorination. Oxidative chlorination is a well known technique, most conveniently operated by introducing chlorine into dilute aqueous hydrochloric acid reaction medium at room temperature or below, with the substance to be chlorinated present in solution or suspension. (See, for example, the publication by Petrow et al. J. Chem. Soc. 198, p. 1508). Amines are known to interfere with the reaction. Consequently a preferred approach to synthesis of the desired class of compounds has involved protection of the free amine group prior to oxidative chlorination, as shown below in the synthesis scheme disclosed in U.S. Pat. No. 4,021,225: ##STR2## wherein the substituents are as defined above.
U.S. Pat. No. 3,824,247 discloses that protection of the amino substituent on the thiadiazole nucleus is unnecessary in the formation of the corresponding sulfonyl chloride by oxidative chlorination of the mercapto substituent.
Ergo, the more direct preferred route in the prior art to the herbicides of this class is performed in the following sequence:
(a) chlorinating under oxidizing conditions a 2-mercapto-4-amino-1,3,4-thiadiazole to yield a corresponding sulfonyl chloride; PA1 (b) reacting said sulfonyl chloride with a secondary amine to yield a corresponding sulfonamide; PA1 (c) reacting said sulfonamide with a carbamyl chloride or isocyanate or preferably reacting the amine substituent with phosgene in inert solvent followed by reacting the resulting carbamyl chloride with an amine to yield the desired phytotoxic ureidothiadiazole-sulfonamide as described above. PA1 R.sup.5 is selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, and C.sub.3 to C.sub.6 cycloalkyl; and PA1 X is oxygen or sulfur.
More specifically, the route to the superior industrial type herbicide 5-[[(dimethylamino)carbonyl]methylamino]-N,N-dimethyl-1,3,4-thiadiazole-2- sulfonamide via the teachings of the '225 patent is as set forth below: ##STR3##
2-mercapto-5-methylamino-1,3,4-thiadiazole (MMT) 1 is converted to the acetyl derivative 2 to protect the methylamino group from the conditions of the subsequent oxidative chlorination. The acetyl derivative 2 is reacted with chlorine in dilute hydrochloric acid to give the sulfonyl chloride 3 which is further reacted with dimethylamine to form the sulfonamide 4. The protecting group is then removed from 4 by reaction with NaOH, resulting in 2-methylamino-1,3,4-thiadiazole-5-N,N-dimethylsulfonamide (MTD) 5.
The improvement disclosed in the '247 patent, based on the discovery that the protecting group was unnecessary and that MMT can be directly oxidatively chlorinated, as specifically applied to the preparation of the above-identified preferred herbicide is shown schematically as follows: ##STR4##
Thus, in this preferred teaching of the prior art, i.e., the disclosure of U.S. Pat. No. 3,824,247, 2-mercapto-5-methylamino-1,3,4-thiadiazole (MMT) 1 is directly oxidatively chlorinated with chlorine in dilute hydrochloric acid to give the sulfonyl chloride 7 which is then reacted with dimethylamine to form the sulfonamide 5. The reported yield of 2-methylamino-1,3,4-thiadiazole-5-N,N-dimethyl sulfonamide (MTD) 5 based on 2-mercapto-5-methylamino-1,3,4-thiadiazole (MMT) 1 from this preferred prior art sequence is 70%.
In both of the afore described reaction schemes, the 2-methylamino-1,3,4-thiadiazole-5-N,N-dimethyl-sulfonamide (MTD) 5 is converted to the herbicidal compound 5[[(dimethylamino)carbonyl]methylamino]-N,N-dimethyl-1,3,4-thiadiazole-2-s ulfonamide 6 by reaction with phosgene and dimethylamine as shown in the schemes.
Following the teachings of the '247 patent which indicated that the oxidative chlorination proceeded by the introduction of chlorine into dilute hydrochloric acid below room temperature, routine experimentation determined that the yield of MTD (5) increased as 0.degree. C. was approached. Therefore, to optimize the '247 teaching a suspension of MMT (1) was formed in aqueous sodium chloride solution to prevent the reaction mixture from freezing as the temperature was lowered to 0.degree. C. and below. As the suspension was stirred vigorously, chlorine (3.1 equivalents based on MMT) was introduced into the reaction mixture in test runs conducted at from 0.degree. C. to -12.degree. C. The resulting sulfonyl chloride was converted to MTD by adding sufficient aqueous dimethylamine to neutralize all of the hydrogen chloride as well as to react with the sulfonyl chloride (7 to 9 equivalents of dimethylamine based on MMT).
The absolute yield of MTD (the yield of the crude product multiplied by the product assay) varied inversely with the temperature at which the oxidative chlorination was conducted and ranged from 84% at -12.degree. C. to 37% at 23.degree. C. A Least Squares Linear Regression Analysis of the data revealed that the sensitivity of the yield to temperature was -1.3%/.degree.C.
A temperature of -5.degree. C. is about the lowest practical temperature for large-scale, commercial equipment for this process and the data indicated that a reaction temperature of -5.degree. C. for the oxidative chlorination of MMT from the improved prior art process would result in a 74% absolute yield of MTD.
Utilizing the process discovery of the instant invention, the yields of MTD can be increased and therefore the cost of manufacturing MTD can be made more favorable; ultimately lowering the manufacturing cost of the highly desirable herbicidal compound 5-[(dimethylamine)carbonyl]methylamino]-N,N-dimethyl-1,3,4-thiadiazole-2-s ulfonamide.
Accordingly, one or more of the following objectives can be achieved by the practice of this invention. It is an object of this invention to increase the yields of certain 1,3,4-thiadiazole-5-sulfonamides which are useful precursors to herbicidal compounds. Additionally it is an object of this invention to specifically increase the oxidative chlorination yield of 2-methylamino-1,3,4-thiadiazole-5-N,N-dimethyl sulfonamide a precursor in the production of 5-[[(dimethylamino)carbonyl]methylamino]-N,N-dimethyl-1,3,4-thiadiazole-2- sulfonamide; an extremely effective herbicide. Those and other objects will readily became apparent to those skilled in the art in the light of the teachings herein set forth.